Multimorbidity of cardiovascular disease subtypes in a prospective cohort of 1.2 million UK women

Objective Cardiovascular multimorbidity (CVM) is the co-occurrence of multiple cardiovascular disease subtypes (CVDs) in one person. Because common patterns and incidence of CVM are not well-described, particularly in women, we conducted a descriptive study of CVM in the Million Women Study, a large population-based cohort of women. Methods UK women aged 50–64 years were followed up using hospital admissions and mortality records for an average of 19 years. CVM was defined as having ≥2 of 19 selected CVDs. The age-specific cumulative incidence of CVM between age 60 and 80 years was estimated. The numbers and proportions of individual, pairs and other combinations of CVDs that comprised incident CVM were calculated. For each individual CVD subtype, age-standardised proportions of the counts of other co-occurring CVDs were estimated. Results The age-specific likelihood of having CVM nearly doubled every 5 years between age 60 and 80 years. Among 1.2 million women without CVD at study baseline, 16% (n=196 651) had incident CVM by the end of follow-up. Around half of all women with CVM had a diagnosis of ischaemic heart disease (n=102 536) or atrial fibrillation (n=96 022), almost a third had heart failure (n=72 186) and a fifth had stroke (n=40 442). The pair of CVDs with the highest age-adjusted incidence was ischaemic heart disease and atrial fibrillation (18.95 per 10 000 person-years). Over 60% of individuals with any given CVD subtype also had other CVDs, after age standardisation. Conclusions CVM is common. The majority of women with any specific CVD subtype eventually develop at least one other. Clinical and public health guidelines for CVD management should acknowledge this high likelihood of CVM.


Participant characteristics
All participant characteristics reported in this study were collected through the self-reported questionnaire completed at recruitment [available from: https://www.ceu.ox.ac.uk/research/million-women-study-1/questionnaires].An event was defined as the first hospital admission after recruitment with a ICD-10 code in any position (i.e.primary or secondary diagnosis fields) or death with the diagnosis as the underlying cause, whichever came first.Only events that were recorded after the date of recruitment up to 31 December 2016 were counted.Note that these were not strictly incident events, since participants with prior CVD at recruitment had not been excluded yet.Note also that end of follow-up when the CVDs were selected was 31 December 2016, whereas the analyses presented in this study included additional follow-up time up to 31 December 2019.Nineteen CVDs with 5,000 or more events by the end of 2016

Table A1. Number and proportion of missing values for key characteristics self-reported at recruitment
were finally included (Table B1).The selected CVDs could be broadly grouped into three disease classes: heart diseases, cerebrovascular diseases, and other vascular diseases.
We acknowledge that some of the CVD subtypes we have defined may not be clearly distinct aetiologically and/or anatomically.For example, the ICD-10 codes that define 'other cerebrovascular disease' encompasses a range of conditions such as 'other nontraumatic intracranial haemorrhage (I62)', 'occlusion and stenosis of precerebral/cerebral arteries, not resulting in cerebral infarction (I65, I66)' or 'cerebral disorders in diseases classified elsewhere (I68)' (e.g.I68.0, cerebral amyloid angiopathy).We acknowledge that these cannot be cleanly separated from stroke and vascular dementia and will largely co-occur with those conditions (which we observe in the data).However, we aimed to include a comprehensive range of CVDs as represented by the ICD-10 coding system and commonly recorded in HES and death records.We therefore chose to include these codes under the umbrella term, 'other cerebrovascular disease'.
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s)  *Diagnostic codes used to identify diseases from hospital admission and death records **An event was defined as the first hospital admission after recruitment with a relevant ICD-10 code in any position or death with the diagnosis as the underlying cause, whichever came first.These were not considered incident events, since women with cardiovascular disease prior to recruitment were not excluded from the cohort yet.
BMJ Publishing Group Limited (BMJ) disclaims all liability and responsibility arising from any reliance Supplemental material placed on this supplemental material which has been supplied by the author(s) cancer registrations came from the Office for National Statistics (ONS), via NHS Digital in England and the Information Services Division (ISD) in Scotland (which has been part of Public Health Scotland since April 2020).Hospital admission data were acquired from the NHS Hospital Episode Statistics in England through NHS Digital, and from the Scottish Morbidity Records in Scotland through ISD Scotland.Nearly 20 years on average after recruitment, only about 1.5% of the Million Women Study cohort was lost to follow-up.

Table B1
List of selected individual cardiovascular corresponding diagnostic codes, and number of events between study recruitment and 31 December 2016, after standard exclusions only